Metastatic breast cancer (MBC) is an incurable but treatable form of breast cancer. It’s also known as stage 4 breast cancer, sometimes written with Roman numerals as stage IV breast cancer. Since the 1800s, doctors and researchers have learned more about how MBC develops and have discovered new ways to treat it. From 1990 to 2010, the life span of people with MBC increased from less than two years to more than three.

New treatments for metastatic breast cancer continue to improve quality of life and increase life expectancy for people with the condition. Treatments focus on stabilizing cancer — preventing progression (when cancer grows and spreads elsewhere in the body). You and your oncologist should work together to choose a treatment that will give you the best quality of life with the fewest side effects.

Read on for an overview of the progression of new MBC treatments that work to improve survival and give people more time with their loved ones.

Chemotherapy

Chemotherapy has been used for decades to treat several types of cancer, including MBC. Chemotherapy drugs work by interfering with cell growth and division in rapidly dividing cells (such as cancer cells). Until the 1960s, cancer treatments were mainly focused on surgery and radiation therapy — however, researchers learned that chemotherapy could better control disease, helping extend survival.

Over the years, doctors and researchers have found that some chemotherapy drugs are especially effective for treating MBC. These include:

• 5-fluorouracil (sold as 5-FU and Adrucil)
• Capecitabine (Xeloda)
• Cyclophosphamide (Cytoxan)
• Docetaxel (Taxotere)
• Doxorubicin (Adriamycin)
• Methotrexate
• Paclitaxel (Abraxane and Taxol)

Studies show that chemotherapy has reduced the risk of death by 7 percent to 33 percent in people with invasive or metastatic breast cancer, according to PLOS One. Today, chemotherapy is often combined with targeted therapies, which aim at different proteins or hormones to make them more effective at treating MBC.

Hormone Therapy

As researchers learned more about breast cancer, they found that some cells rely on hormones like estrogen or progesterone to grow. These hormones bind to receptors on the outside of cells, telling them to grow and divide rapidly. Your doctor may classify your MBC as estrogen receptor (ER)-positive or progesterone receptor (PR)-positive if you have these receptors on your breast cancer cells.

With this discovery, researchers developed targeted therapies to block these receptors and effectively stop breast cancer cells from growing. In 1977, the U.S. Food and Drug Administration (FDA) approved tamoxifen, the first anti-estrogen drug for treating breast cancer. More than 50 percent of people with hormone receptor (HR)-positive breast cancer who take tamoxifen see their cancer stabilize, according to UpToDate. However, some people don’t respond to the medication at all.

These drugs, called aromatase inhibitors, are used to reduce estrogen in the body, and they’ve proved effective in treating ER-positive metastatic breast cancers. This class of drugs includes:

• Anastrozole (Arimidex)
• Letrozole (Femara)
• Exemestane (Aromasin)

Another hormone therapy — Faslodex (a formulation of fulvestrant) — was approved by the FDA in 2002 for treating hormone-sensitive breast cancer. In 2017, the FDA expanded the drug’s approval to include postmenopausal women with HR-positive MBC.

Per the National Cancer Institute, one study showed that fulvestrant stopped MBC progression for 16.6 months, compared to only 13.8 months with the drug anastrozole. This means that fulvestrant helped people live longer with stable disease compared to anastrozole.

HER2 Therapies

In some cases, breast cancer cells make too much of a protein called human epidermal growth factor receptor 2 (HER2). Previously, people with HER2-positive MBC were treated with chemotherapy. A clinical trial comparing trastuzumab (Herceptin) to standard chemotherapy found that trastuzumab helped to better stabilize their disease. On average, people who received trastuzumab lived longer than those who received chemotherapy. The FDA approved Herceptin in 1998.

Some cancer therapies also work better in combination with others than they do on their own. In 2012, the FDA approved the HER2 drug Perjeta, a formulation of pertuzumab, for use with trastuzumab and chemotherapy in people with HER2-positive MBC. A study published in The New England Journal of Medicine showed that this combination helped people live nearly 16 months longer than trastuzumab and chemotherapy alone.

In 2022, the FDA approved a formulation of fam-trastuzumab deruxtecan-nxki called Enhertu as the first treatment for people with MBC with low levels of HER2. Fam-trastuzumab delivers chemotherapy directly to cancer cells. Studies show that it stabilized disease more, according to the FDA, helping people live nearly seven months longer than chemotherapy alone.

Tyrosine Kinase Inhibitors

Tyrosine kinases are specialized proteins that send signals for cancer cells to grow and divide. Breast cancer cells can make too many of these proteins, causing them to grow out of control. Medications known as tyrosine kinase inhibitors (TKIs) block this uncontrolled cell growth.

The first TKI approved by the FDA for treating HER2-positive MBC was Tykerb, a formulation of lapatinib. The FDA approved the drug in 2007 in combination with capecitabine.

In 2020, the FDA approved two more TKIs — Nerlynx, a formulation of neratinib, and Tukysa, a formulation of tucatinib. Clinical trials found that both drugs stopped cancer progression for longer than the currently available therapies did, helping people to live longer.

Cyclin-Dependent Kinase 4/6 Inhibitors

Cyclin-dependent kinase (CDK) 4/6 inhibitors, another fairly new class of medications, block the enzymes CDK4 and CDK6. These medications interfere with breast cancer cell division, stopping cells from replicating. In 2015, the FDA began approving CDK4/6 inhibitors to treat HER2-negative MBC, including:

• Ibrance (a formulation of palbociclib) — In clinical trials, the drug prevented cancer progression for 10 months longer compared to controls, according to the FDA.
• Verzenio (a formulation of abemaciclib) — This drug prevented cancer progression for seven months longer compared to controls in clinical trials, per the FDA.
• Kisqali (a formulation of ribociclib) — In clinical trials, 70 percent of people taking ribociclib were alive after 42 months, compared to 46 percent of people taking hormone therapy alone, according to the National Cancer Institute.

PI3 Kinase Inhibitors

Phosphoinositide 3-kinase (PI3K) inhibitors can be used to treat cancers with the PIK3CA gene mutation. A formulation of alpelsib called Piqray is FDA-approved.

PARP Inhibitors

Some breast cancers are caused by mutations in the BRCA1 and BRCA2 genes, which normally work to help repair damaged DNA. Researchers have developed new medications specifically to treat people with HER2-negative MBC with BRCA1 and 2 mutations. These are known as poly (ADP-ribose) polymerase (PARP) inhibitors.

In 2018, the FDA approved the PARP inhibitors Lynparza (a formulation of olaparib) and Talzenna (a formulation of yalazoparib) for treating people with MBC who had been previously treated with chemotherapy. Both medications were shown to prevent cancer from progressing longer than chemotherapy, helping participants live longer with stable disease.

Checkpoint Inhibitors

Some breast cancer cells have a protein known as PD-L1 on their surface that helps them hide from your immune system. Checkpoint inhibitors are a type of immunotherapy that blocks PD-L1, helping your immune system recognize cancer.

In 2020, the FDA approved Keytruda, a formulation of pembrolizumab, with chemotherapy to treat metastatic triple-negative breast cancer that’s positive for PD-L1. This combination was shown to nearly double the time to cancer progression compared to treatment with a placebo (“fake” drug) and chemotherapy, according to the FDA.

Promising Treatments for MBC

As we continue to learn more about MBC, doctors and researchers look for new ways to treat it. Sometimes they develop entirely new drugs that target breast cancer in a novel way, while other studies are focused on finding ways to repurpose currently available therapies.

Some new treatments currently being studied in laboratories or in clinical trials in people with MBC include:

• Medications that block androgen receptors (similar to ER and PR) to slow breast cancer cell growth
• Medications that block CDK7 to interrupt cancer cell division
• New types of PARP inhibitors, antibody-drug conjugates, and antiestrogen therapies

If you’re interested in learning more about new treatments for MBC, talk to your oncologist. Clinical trials are an option for those looking to try an experimental therapy that may be beneficial.

Talk With Others Who Understand

MyBCTeam is the social network for people with breast cancer and their loved ones. On MyBCTeam, more than 61,000 members come together to ask questions, give advice, and share their stories with others who understand life with breast cancer.

Are you living with metastatic breast cancer? Share your experience in the comments below, or start a conversation by posting on your Activities page.